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Fixing frataxin: 'ironing out' the metabolic defect in Friedreich's ataxia.

Authors
  • Anzovino, A
  • Lane, D J R
  • Huang, M L-H
  • Richardson, D R
Type
Published Article
Journal
British Journal of Pharmacology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Apr 01, 2014
Volume
171
Issue
8
Pages
2174–2190
Identifiers
DOI: 10.1111/bph.12470
PMID: 24138602
Source
Medline
Keywords
License
Unknown

Abstract

The metabolically active and redox-active mitochondrion appears to play a major role in the cellular metabolism of the transition metal, iron. Frataxin, a mitochondrial matrix protein, has been identified as playing a key role in the iron metabolism of this organelle due to its iron-binding properties and is known to be essential for iron-sulphur cluster formation. However, the precise function of frataxin remains elusive. The decrease in frataxin expression, as seen in the inherited disorder Friedreich's ataxia, markedly alters cellular and mitochondrial iron metabolism in both the mitochondrion and the cell. The resulting dysregulation of iron trafficking damages affects tissues leading to neuro- and cardiodegeneration. This disease underscores the importance of iron homeostasis in the redox-active environment of the mitochondrion and the molecular players involved. Unravelling the mechanisms of altered iron metabolism in Friedreich's ataxia will help elucidate a biochemical function for frataxin. Consequently, this will enable the development of more effective and rationally designed treatments. This review will focus on the emerging function of frataxin in relation to the observed alterations in mitochondrial iron metabolism in Friedreich's ataxia. Tissue-specific alterations due to frataxin loss will also be discussed, as well as current and emerging therapeutic strategies.

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